Difference between the transactions ME25 and ME21N

ME25 is useful when you want to create a PO but you are unsure if there is a valid source or if there is, which one to use.

With ME21N you have to specify the Vendor before you can do anything and so you must know the vendor when you start.

With ME25 you can enter all of the details and leave the vendor until last and use auto source determination if you want. Then if you still cannot find a source you can save it as a requisition instead and find and allocate a source later.

So if you KNOW the vendor that you are going to use, then create the PO via ME21N.

If you DON'T KNOW (or are not sure) of the vendor to be used (and if your company allow the use of this transaction), use ME25 instead.